纤连蛋白是一种大脑血管结构特异性基因并在胶质瘤中异常高表达  

High and specific expression of Fibronectin(FN1)in cerebral vascular cells as an abnormal expression in glioma tumor cells

作　　者：明安红 朱梦婷 吕瑞 姬昂 薛小燕 章翔 毛星刚 MING Anhong;ZHU Mengting;LYU Rui;JI Ang;XUE Xiaoyan;ZHANG Xiang;MAO Xinggang(Department of Neurosurgery,Xijing Hospital,Fourth Military Medical University,Xi'an,Shaanxi 710032,China;No3 Cadet Regiment,School of Basic Medical Sciences,Fourth Military Medical University,Xi'an,Shaanxi 710032,China;Department of Pharmacology,School of Pharmacy,Fourth Military Medical University,Xi'an,Shaanxi 710032,China)

机构地区：[1]空军军医大学西京医院神经外科,陕西西安710032 [2]空军军医大学基础医学院学员三大队,陕西西安710032 [3]空军军医大学药学系药理学教研室,陕西西安710032

出　　处：《中华神经外科疾病研究杂志》2024年第3期1-7,共7页Chinese Journal of Neurosurgical Disease Research

基　　金：国家自然科学基金资助项目(81972359,82273978)。

摘　　要：目的研究细胞外基质(ECM)中的重要蛋白—纤连蛋白(FN1)在正常脑组织及胶质瘤中的表达模式,特别是在不同类型细胞中的表达情况。方法根据单细胞测序数据,分析在正常人类和小鼠大脑组织中,FN1在不同类型细胞中的表达情况。进一步分析胶质母细胞瘤(GBM)单细胞测序数据中,FN1在不同类型细胞中的表达。最后,通过免疫组化染色的结果,研究FN1蛋白在正常大脑及胶质瘤组织中的表达,特别是在血管结构的表达。结果在人类和小鼠的单细胞测序数据分析中,FN1有一致的表达模式,都是特异性的高表达于血管结构细胞,包括血管内皮细胞和血管周细胞。而在GBM的单细胞测序数据中,FN1不仅高表达于血管内皮和周细胞,还高表达于肿瘤细胞等其他类型的细胞,包括胶质瘤干细胞(GSC)、免疫细胞等。进一步的免疫组化染色结果证实了FN1在正常大脑高表达于血管结构,而在高级别胶质瘤中,除高表达于血管结构外,还高表达于肿瘤细胞。结论FN1在正常大脑组织是一类在血管结构特异性高表达的分子,而在GBM中,则异常表达于肿瘤细胞、干细胞、免疫细胞等,反应了GBM肿瘤细胞的高度异质性和可塑性。Objective To investigate the expression patterns of fibronectin(FN1),an important protein in the extracellular matrix(ECM),in normal brain tissue and gliomas,with special attention to its expression in different types of cells.Methods Single-cell sequencing data were used to analyze the expression of FN1 in different types of cells in normal human and mouse brain tissues.Further analysis of single-cell sequencing data in glioblastoma(GBM)was performed.Finally,the expression of FN1 protein in normal brain and glioma tissues,especially in vascular structures,was studied by immunohistochemical staining.Results In both human and mouse normal brain single-cell sequencing data,FN1 showed consistent expression patterns and was specifically overexpressed in vascular structural cells,including endothelial cells and pericytes.In the single-cell sequencing data of GBM,FN1 was not only highly expressed in vascular endothelium and pericytes,but also in other types of cells such as tumor cells,including glioma stem cells(GSC),immune cells,etc.Further immunohistochemical staining results confirmed that FN1 protein is highly expressed in vascular structures in the normal brain,while in high-grade gliomas,it is also highly expressed in tumor cells in addition to vascular structures.Conclusion FN1 is a type of molecule that is highly expressed in vascular structure in normal brain tissue,while in GBM,it is abnormally expressed in tumor cells,stem cells,immune cells,etc.,reflecting the high heterogeneity and plasticity of GBM tumor cells.

关 键 词：胶质母细胞瘤 内皮细胞 周细胞 血管结构 血管 巨噬细胞 小胶质细胞 肿瘤干细胞 

分 类 号：R739.41[医药卫生—肿瘤]